Date Published:

Dec 1

Abstract:

Osteosarcoma (OS) is an aggressive malignancy affecting mostly children and adolescents. MicroRNAs (miRNAs) play important roles in OS development and progression. Here we found that miR-16-1-3p and miR-16-2-3p "passenger" strands, as well as the "lead" miR-16-5p strand, are frequently downregulated and possess strong tumor suppressive functions in human OS. Furthermore, we report different although strongly overlapping functions for miR-16-1-3p and miR-16-2-3p in OS cells. Ectopic expression of these miRNAs affected primary tumor growth, metastasis seeding and chemoresistance and invasiveness of human OS cells. Loss-of-function experiments verified tumor suppressive functions of these miRNAs at endogenous levels of expression. Using RNA immunoprecipitation (RIP) assays, we identify direct targets of miR-16-1-3p and miR-16-2-3p in OS cells. Moreover, validation experiments identified FGFR2 as a direct target for miR-16-1-3p and miR-16-2-3p. Overall, our findings underscore the importance of passenger strand miRNAs, at least some, in osteosarcomagenesis.

Notes:

Maximov, Vadim VAkkawi, RaniaKhawaled, SalehSalah, ZaidounJaber, LinaBarhoum, AhlamOr, OmerGalasso, MarcoKurek, Kyle CYavin, EylonAqeilan, Rami IengResearch Support, Non-U.S. Gov'tInt J Cancer. 2019 Dec 1;145(11):3052-3063. doi: 10.1002/ijc.32368. Epub 2019 May 9.

PubMed